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Purpose. Ultraviolet radiation (UVR) is one of the exogenous stimuli increasing melanogenesis. UV light, especially UVB, is also a potent inducer of epidermal cytokine release. This study is aimed at determining the underlying mechanisms by which UVB-induced cytokines in keratinocytes regulate melanin production in vitro. Methods. Expression levels of mRNA for interleukin- (IL-) 1, IL-1β, IL-6, IL-10, IL-17, and tumor necrosis factor-alpha (TNF-α) were measured using RT-qPCR at various time points after UVB irradiation in C57BL/6 mice and HaCaT cells. NaOH lysis and L-dihydroxyphenylalanine (L-DOPA) oxidation method were used to measure melanin content and tyrosinase (TYR) activity, respectively, in melanoma B16 cells. RT-qPCR and Western blot were used to assess mRNA and protein levels of microphthalmia-associated transcription factor (MITF), TYR, tyrosine-related protein-1 (TRP-1), and tyrosine-related protein-2 (TRP-2) in B16 cells. Finally, expression levels of cyclooxygenase-2 (COX-2) mRNA and stem cell factor (SCF) in HaCaT cells were measured following knockdown of IL-1β using siRNA (siIL-1β). Results. UVB irradiation increased IL-1β mRNA expression levels in both C57BL/6 mice and HaCaT cells. The melanin content, TYR activity, and expression levels of TYR and TRP-1 were all raised when B16 cells were treated with 4 pg/l of IL-1. Moreover, IL-1β also upregulated the expression levels of SCF and COX-2 in nonirradiated HaCaT cells. Conversely, knockdown of IL-1β attenuated UVB irradiation-induced upregulation of SCF and COX-2 expression in keratinocytes. Conclusions. UVB-induced melanogenesis is mediated in part by IL-1β, leading to upregulation of the TYR/TRP1 expression in melanoma B16 cells. IL-1β can also stimulate the expression of COX-2 and SCF in HaCaT cells, which in turn increase melanin synthesis in melanocytes. These results suggest that anti-inflammatory approaches could possibly mitigate UVB-induced hyperpigmentation.

Nitric oxide (NO), a signaling molecule, regulates biological functions in multiple organs/tissues, including the epidermis, where it impacts permeability barrier homeostasis, wound healing, and antimicrobial defense. In addition, NO participates in cutaneous inflammation, where it exhibits pro-inflammatory properties via the cyclooxygenase/prostaglandin pathway, migration of inflammatory cells, and cytokine production. Yet, NO can also inhibit cutaneous inflammation through inhibition of T cell proliferation and leukocyte migration/infiltration, enhancement of T cell apoptosis, as well as through down-regulation of cytokine production. Topical applications of NO-releasing products can alleviate atopic dermatitis in humans and in murine disease models. The underlying mechanisms of these discrepant effects of NO on cutaneous inflammation remain unknown. In this review, we briefly review the regulatory role of NO in cutaneous inflammation and its potential, underlying mechanisms.

Importance Patients with atopic dermatitis (AD) display compromised epidermal barrier and suffer from poor quality of life. We hypothesized that quality of life could reflect in the changes in the epidermal barrier function. Objective To determine whether the epidermal barrier function correlates with the severity of pruritus and/or life quality in children with AD. Methods A total of 120 children, aged 0–12 years, with moderate AD were enrolled. Children were topically treated with topical corticosteroids (TCS) and an emollient for 2 weeks. The Eczema Area and Severity Index (EASI), visual analogue scale (VAS) for pruritus severity, the Infant’s Dermatitis Quality of Life Index (IDQOL) and the Children’s Dermatology Life Quality Index (CDLQI) were evaluated. Transepidermal water loss (TEWL) rates, stratum corneum (SC) hydration, and skin surface pH were measured. Correlations of epidermal barrier function with pruritus, life quality, and EASI were determined. Results Following 2‐week treatments, significant improvements were observed in EASI, TEWL, SC hydration, the VAS of pruritus, as well as DQOL (P < 0.001 for all). TEWL positively, while SC hydration negatively correlated with VAS pruritus, DQOL, and EASI (P < 0.001). Interpretation Both TEWL and SC hydration levels can serve as indicators of the severity of pruritus and quality of life in children with AD., This study suggests that the epidermal barrier function correlates with the severity of pruritus and/or life quality in children with atopic dermatitis. It also suggests that either transepidermal water loss rates (TEWL) or stratum corneum (SC) hydration levels can serve as an indictor of visual analogue scale pruritus, dermatitis quality of life index (DQOL) in children with atopic dermatitis.

Epidermal function is regulated by numerous exogenous and endogenous factors, including age, psychological stress, certain skin disorders, ultraviolet irradiation and pollution, and epidermal function itself can regulate cutaneous and extracutaneous functions. The biophysical properties of the stratum corneum reflect the status of both epidermal function and systemic conditions. Type 2 diabetes in both murine models and humans displays alterations in epidermal functions, including reduced levels of stratum corneum hydration and increased epidermal permeability as well as delayed permeability barrier recovery, which can all provoke and exacerbate cutaneous inflammation. Because inflammation plays a pathogenic role in type 2 diabetes, a therapy that improves epidermal functions could be an alternative approach to mitigating type 2 diabetes and its associated cutaneous disorders.表皮功能受到多种外源性和内源性因素的调节，包括年龄、心理应激、某些皮肤病、紫外线照射和污染，而表皮本身也可以调节皮肤和皮外的功能。角质层的生物和物理性质反映了表皮功能和全身状况。在小鼠模型和人类中，2型糖尿病都表现出表皮功能的变化，包括角质层水合作用水平降低、表皮渗透性增加、以及通透性屏障恢复延迟，这些都可以引发和加剧皮肤炎症。由于炎症在2型糖尿病中起致病作用，因此改善表皮功能的治疗可能是缓解2型糖尿病及其相关皮肤疾病的替代方法。.

To evaluate the efficacy and safety of 755 nm Q-Switched alexandrite laser for Hori’s nevus in a large cohort of Chinese women. We retrospectively analyzed the efficacy and safety of 755 nm Q-Switched alexandrite laser for Hori’s nevus. Reduction in pigment was evaluated using a 4-score method. A total of 482 patients, aged 16 to 52 years, were included in this analysis. Patients were treated with 755 nm Q-Switched alexandrite laser at fluence levels of 5–8 J/cm2 for 2–4 treatment sessions. Following the treatments, 53% of patients showed over 75% reductions in pigment while 50–75% reductions in pigment were observed in 28% of patients. The rest displayed less than 50% improvements. Efficacy was positively correlated with the number of treatment sessions (p

Xiaohua Wang,1,* Qingsong Lai,2,* Baoqing Zheng,1 Li Ye,1 Si Wen,1 Yunling Yan,1 Bin Yang,1 Mao-Qiang Man1 1Dermatology Hospital, Southern Medical University, Guangdong, 510091, People’s Republic of China; 2Center for Chronic Disease Prevention and Control of Puning City, Puning, Guangdong, 515300, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mao-Qiang Man; Bin YangDermatology Hospital, Southern Medical University, 2 Lujing Road, Yuexiu District, Guangzhou, Guangdong, 510091, People’s Republic of ChinaEmail mqman@hotmail.com; yangbin101@hotmail.comBackground: Although the characteristics of pruritus in some skin diseases are documented, characteristics of pruritus related to gender-, age-, and skin disorder have not yet been well defined.Objective: To characterize dermatosis-associated pruritus in Chinese patients.Methods: A cross-sectional study was carried out in a single center. The intensity of pruritus was evaluated using a 0– 10 visual analog scale (VAS). Skin disorders were diagnosed by dermatologists. The prevalence and intensity of pruritus were compared among skin disorders, and between males and females.Results: Valid questionnaires were obtained from 1,246 female and 864 male patients. Patients with acne, eczematous dermatitis, and urticaria accounted for 18%, 17%, and 14%, respectively. Both the prevalence and severity of pruritus varied greatly with skin disorders (p< 0.0001). Patients with either urticaria or eczematous dermatitis displayed a higher prevalence of pruritus (92% and 82%, respectively), while subjects with urticaria exhibited the highest VAS in comparison to those with other skin disorders (p< 0.05 to p< 0.001 vs the others). Moreover, both the prevalence and severity of pruritus were positively associated with age in both males and females (p< 0.0001). Furthermore, 60 out of 77 patients (78%) with topical glucocorticoid-induced dermatitis experienced pruritus, with a VAS of 2.03± 0.21. Finally, a lower VAS was found in subjects with oily skin than those with either dry or normal skin.Conclusion: The prevalence and severity of pruritus vary with skin disorders, skin type, age, and gender in Chinese patients.Keywords: skin disorder, pruritus, prevalence, severity, gender, age

OBJECTIVE To determine whether topical applications of thiosulfinate-enriched Allium sativum extract (TASE) can accelerate acute cutaneous wound healing (WH) in a murine model. METHODS Keratinocyte viability and in vitro wound closure were assessed in keratinocyte cultures. Effects of topical TASE (0.5 μg/mL of allicin in 97% ethanol) on acute cutaneous WH were determined in a murine model of acute cutaneous wound. Twelve mice were alternately assigned to the vehicle- and TASE-treated groups (n=6 per group). Expression levels of mRNA for keratinocyte differentiation marker-related proteins (filaggrin, loricrin and involucrin) and lipid synthetic enzymes (elongation of very long chain fatty acids protein 4 (ELOVL4), fatty acid synthase (FA2H), 3-hydroxy- 3-methyl-glutaryl-coenzyme A reductase (HMGCoA), and serine palmitoyltransferase (SPT)) were assessed using real-time quantitative polymerase chain reaction on day 3 and 8 after wounding, while transepidermal water loss (TEWL) rates were measured in wounded areas. RESULTS TASE accelerated WH both in vivo (40% vs. 22% reduction in wound area, P

Background/Aim Although the characteristics of cutaneous sensory symptoms in the general population have been documented, dermatological condition-associated skin pain has not been characterized yet. In the present study, we aimed to characterize dermatological condition-associated skin pain in the Chinese. Subjects and Methods A questionnaire was given to outpatients to identify self-proclaimed skin pain at our dermatology clinic. The severity of skin pain was assessed using pain scale 0-10. Prevalence and pain severity were compared between males and females. Results A total of 2144 patients, including 1254 females and 890 males aged 13-94 years, were included in this study. The overall prevalence of skin pain was 9.93% in this cohort. The prevalence of skin pain varied greatly with dermatological conditions (p

Although a compromised epidermal permeability barrier can contribute to the development of contact dermatitis, whether subjects with hand eczema display abnormalities in baseline epidermal permeability barrier function in their uninvolved skin remains unknown. The aim of the present study was to assess epidermal permeability barrier function in subjects with and without hand eczema in clothing manufacturers. Upon approval by the institutional review board, volunteers were recruited from clothing manufacturers in Guangzhou City, China. An 11-item questionnaire was used to collect general data from the volunteers. The diagnoses of self-proclaimed hand eczema were further confirmed by a dermatologist. Epidermal biophysical properties, including transepidermal water loss (TEWL) rates, stratum corneum hydration and skin surface pH were measured on the flexural surface of the left forearm in all volunteers. Epidermal biophysical properties were compared among cohorts of subjects with active hand eczema, a prior history of hand eczema and without any history of hand eczema. A total of 650 questionnaires were collected from 462 females and 188 males, with a mean age of 36.7 ± 0.46 years (range 16–69 years; 95% CI 35.8–37.59). Thirty-five subjects (5.4%) currently had hand eczema, while 28 subjects (4.3%) reported a prior history of hand eczema that was inactive currently. The prevalence of hand eczema did not differ significantly between genders. Neither a prior personal nor a family history of allergies was associated with the prevalence of hand eczema, but certain occupations and frequent contact with disinfectants were independently associated with the prevalence of hand eczema. In the overall cohort, males displayed higher TEWL rates and stratum corneum hydration levels than did females. Both skin surface pH and TEWL rates differed significantly among normal controls and subjects with active hand eczema or a prior history of hand eczema (p < 0.05). In conclusion, the uninvolved skin site of subjects with hand eczema exhibits abnormalities in epidermal perme­ability barrier, supporting a pathogenic role of epidermal dysfunction in hand eczema. Whether subjects with hand eczema in other occupations also display altered epidermal function on uninvolved skin remains to be explored.

Background: Epidermal function is associated with diabetes and renal disease. Whether obesity can reflect the changes in epidermal function is not clear yet. Objective: We assessed here the correlation of epidermal functions with body mass index (BMI) in a large Chinese cohort. Methods and Subjects: A total of 1,405 Chinese aged 21–98 years old were enrolled in this study. Epidermal functions, including transepidermal water loss (TEWL), stratum corneum hydration, and skin surface pH, were measured on the flexor forearm and the shin. Subjects’ height and body weight were also measured. Results: Age positively correlated with both TEWL and skin surface pH, while it negatively correlated with stratum corneum hydration on both the forearm and the shin of females. Similarly, age positively correlated with skin surface pH, while negatively correlating with stratum corneum hydration on both the forearm and the shin of males. In females, BMI positively correlated with skin surface pH, while it negatively correlated with stratum corneum hydration on both the forearm and the shin. However, BMI correlated neither with skin surface pH on both the forearm and the shin nor with stratum corneum hydration on the shin of males. Conclusion: These results demonstrate that correlations of BMI with age and epidermal functions vary with gender.

Xiaohua Wang,1,2 Si Wen,2 Li Ye,2 Dan Liu,2 Mao-Qiang Man,2 Bin Yang1,2 1Department of Dermatology, Jinan University, Guangzhou City, Guangdong Province, People’s Republic of China; 2The Dermatology Hospital, Southern Medical University, Guangdong, 510091, People’s Republic of ChinaCorrespondence: Bin YangThe Dermatology Hospital, Southern Medical University, 2 Lujing Road, Guangzhou, 510091, People’s Republic of ChinaEmail yangbin1@smu.edu.cnIntroduction: Although it is well known that epidermal function changes with aging, the transcriptomic basis and possible signaling pathways for aging-associated functional changes remain largely unknown.Methods: Here, we employed RNA sequencing techniques to assess epidermal gene expression profiles in the epidermis of mice aged 1, 2, 6, 12 and 20 months.Results: A total of 132 genes displayed reductions in expression levels with aging, while expression levels of 406 genes increased with aging. Epidermal gene expression was prominently upregulated in 2-month-old vs 1-month-old mice, while more genes were downregulated in 12-month-old mice. Upregulation of genes associated with immune/inflammatory responses was observed in the epidermis of aged mice in comparison to that of young mice, whereas downregulated signaling pathways in the epidermis of aged mice were primarily involved in metabolism, such as fatty acid elongation, glutathione metabolism and biosynthesis of antibiotics. Some signaling pathways, such as chemokine signaling, cytokine/cytokine receptor interaction signaling and IL-17 signaling pathways, were remarkably upregulated in 12-month-old mice. Steroid synthesis, metabolic pathway, thermogenesis and proteasome pathways were steadily downregulated, starting at 2 months old.Conclusion: These results indicate that the epidermis of aged mice displays an upregulation of genes associated with inflammatory signaling pathways, and downregulation of genes related to metabolic signaling pathways.Keywords: aging, epidermis, gene expression

Aged humans display a chronic and low-grade inflammation, termed "inflammaging", which has been potentially linked to the subsequent development of some aging-associated systemic disorders, including type 2 diabetes, atherosclerotic cardiovascular disease, Alzheimer's disease and obesity. Though the origin of aging-associated systemic inflammation is uncertain, epidemiological studies show that inflammatory dermatoses (psoriasis and eczema) are risk factors for some aging-associated systemic disorders, such as type 2 diabetes and atherosclerotic cardiovascular disease. Moreover, recent studies demonstrate that epidermal dysfunction in aged skin not only causes cutaneous inflammation, but also a subsequent increase in circulating levels of proinflammatory cytokines, suggesting that the skin could be a major contributor to inflammaging. This hypothesis is further supported by reductions in circulating levels of proinflammatory cytokines in both aged humans and murine, following improvements in epidermal function with topical emollients. Therefore, correction of epidermal dysfunction could be a novel approach for the prevention and mitigation of certain inflammation-associated chronic disorders in aged humans.

Nitric oxide (NO), a signaling molecule, regulates biological functions in multiple organs/tissues, including the epidermis, where it impacts permeability barrier homeostasis, wound healing, and antimicrobial defense. In addition, NO participates in cutaneous inflammation, where it exhibits pro-inflammatory properties via the cyclooxygenase/prostaglandin pathway, migration of inflammatory cells, and cytokine production. Yet, NO can also inhibit cutaneous inflammation through inhibition of T cell proliferation and leukocyte migration/infiltration, enhancement of T cell apoptosis, as well as through down-regulation of cytokine production. Topical applications of NO-releasing products can alleviate atopic dermatitis in humans and in murine disease models. The underlying mechanisms of these discrepant effects of NO on cutaneous inflammation remain unknown. In this review, we briefly review the regulatory role of NO in cutaneous inflammation and its potential, underlying mechanisms.

Disruption of epidermal permeability barrier induces an increase in proinflammatory cytokine expression and release, stimulation of epidermal lipid and DNA synthesis, and expression of antimicrobial peptides. Although alterations in epidermal function in the aged skin are known, whether the epidermal transcriptomic responses to barrier disruption differ between aged and young mice remains unknown. Here, we performed RNA sequencing of the epidermis in 2-month- vs. 20-month-old mice following barrier disruption with repeated tape-stripping. At baseline condition, the epidermis of 20-month-old mice displayed an upregulation of inflammation-associated genes and down-regulation of epidermal structure- and development-related genes in comparison to 2-month-old mice. Barrier disruption upregulated expression levels of 327 genes and downregulated 209 genes in 2-month-old mice. In 20-month-old mice, the numbers of upregulated and down-regulated genes were 537 and 299, respectively. In comparison to young mice, the prominently upregulated genes in the 20-month-old mice were associated with the IL-17 signalling pathway, while downregulated genes were mainly involved in the cytokine-cytokine receptor interaction pathway. These results indicate that inflammation-associated signalling pathways are upregulated, while epidermal structure- and development-related genes are downregulated in the epidermis of aged mice, with further aggravation following barrier disruption, suggesting the importance of improving epidermal function in the elderly.

Background While clinical signs, symptoms, as well as etiology of sensitive skin in general populations have been extensively studied over the last decades, characteristics of sensitive skin in normal subjects, particularly gender-related characteristics, still remain unknown. Objective In the present study, we characterize facial sensitive skin in normal young Chinese. Subjects and methods A questionnaire was given to each participant aged 10-30 years. Clinical signs, symptoms, and associated trigger factors of facial sensitive skin were compared in normal young Chinese males versus females. Results After excluding subjects with pre-existing skin disorders, 475 females and 429 males out of 954 responders were included in the analyzes. Prevalence of self-reported facial sensitive skin was significantly higher in females than in males. Yet, while more females experienced various symptoms, symptoms were more severe in males than in females. However, both the prevalence and severity of clinical signs were similar in females and males. Skin care products appeared to be the major contributors to facial sensitive skin in both genders. Moreover, it appeared that females were more sensitive to environmental factors such as low humidity and sun-exposure while males were more sensitive to emotional factors. Taken together, these results demonstrate that characteristics of sensitive skin are associated with gender, while the underlying mechanisms remain to be explored. Conclusions There are gender differences in prevalence, symptoms, and trigger factors of facial sensitive skin in normal young Chinese.

Summary Background Melasma is an acquired, common hyperpigmented disorder on the face. While many therapeutic approaches are available, their efficacy is moderate. Objective To investigate the safety and efficacy of a cream containing herbal mixture for melasma. Methods A total of 90 volunteers with melasma were enrolled in this randomized, double‐blind, controlled clinical study, and they were randomly divided into three groups (A, B, and C). Patients in group A were treated with a cream containing herbal mixture, while groups B and C were treated with arbutin cream and placebo, respectively, twice daily for 12 weeks. Melasma area and severity index (MASI) score, melanin index (MI), erythema index (EI), changes in density of inflammatory cells, and adverse events were evaluated every 4 weeks. Results Although MASI scores declined significantly in both groups A and B (P

BACKGROUND: Becker’s nevus is a common pigmented dermatosis, usually featured by ipsilateral pigmented patch with hypertrichosis. Becker’s nevus is often treated with various types of lasers although other regimens are available. However, clinical outcomes appear inconsistent among studies. OBJECTIVE: To summarize the clinical outcomes of Becker’s nevus treated with lasers via literature review. RESULTS: A variety of lasers had been used alone or in combination to treat Becker’s nevus. Laser wavelengths used for Becker’s nevus ranged from 504 nm to 10600 nm, while the number of treatment varied from 1 to 12 sessions. The clinical outcomes were mixed although combination of lasers with different wavelengths appeared to achieve a better efficacy. Adverse effects were usually mild to moderate erythema. CONCLUSION: While lasers are relatively safe, their efficacy for Becker’s nevus is moderate. It seems that combination therapy could improve the outcome. However, trials in larger group of patients are required to validate the efficacy of each type of lasers for Becker’s nevus.

Background Rosacea is a common chronic inflammatory dermatosis with uncertainty of etiology. Although clinical features and risk factors of the disease in Caucasians have been reported, this information in Chinese is largely unavailable. Aims To analyze the clinical features and associated risk factors of rosacea in Chinese. Methods A questionnaire was given to outpatients with rosacea who visited the dermatology department of the first affiliated hospital of Kunming Medical University from June 2018 to March 2019. Analyses included demographic characteristics of subjects, clinical characteristics, and risk factors of rosacea. Results A total of 254 outpatients completed the questionnaire. The ratio of female to male was 5.68:1.00. The mean age at onset was 31.18 ± 10.23 years. Erythematotelangiectatic subtype accounted for 51.60%, while 39% of the subjects were of papulopustular subtype. The rest were phymatous type (9.40%). Subjects with flushing, persistent facial erythema, and telangiectasia accounted for 91.73%, 90.55%, and 83.07%, respectively. One hundred and thirteen subjects (44.49%) had papules or pustules, and 24 subjects (9.40%) were with phymatous changes. The most commonly involved sites were the cheeks (93.31%), followed by the nose (82.68%), the perioral area (61.42%), and the forehead (51.97%). The clinical symptoms included burning (93.70%), dryness (90.55%), and itching (75.59%). The main risk factors were sun exposure (90.94%), temperature change (87.40%), etc. Fifty-one (20.08%) patients had comorbidities. Conclusions Rosacea mainly affects young females. The common signs and symptoms include flushing, persistent facial erythema, and burning. Sun exposure and temperature changes are the common risk factors. Patients can have comorbidities of systemic disorders.

The benefits of emollients for eczematous dermatitis and psoriasis have been thought to be due to the improvements in epidermal function, including epidermal permeability barrier, stratum corneum hydration, and stratum corneum pH. We determined here whether emollient can direct inhibit cutaneous inflammation. Ear inflammation was induced by topical application of either 12-O-tetradecanoylphorbol-13-acetate (TPA) or 1-fluoro-2,4-dinitrofluorobenzene (DNFB). Either 1% hydrocortisone cream or the novel emollient was applied to the right ear of the mice 45 min and 2 hours after TPA or DNFB application. The untreated left ear served as untreated controls. Both ear weight and ear thickness were measured 24 hours after TPA and DNFB application. Topical applications of either hydrocortisone cream or emollient significantly decreased both ear thickness and ear weight in comparison to untreated controls. In DNFB model, hydrocortisone significantly lowered expression levels of mRNA for IL-1α, IL-1β, and TNFα, while the emollient markedly decreased expression levels of IL-1α and TNFα mRNA. In TPA model, both hydrocortisone and emollient significantly decreased expression levels of IL-1α, IL-1β, IL-6, and TNFα mRNA. In parallel, inflammatory infiltration was also reduced by topical applications of either hydrocortisone or emollient. These results demonstrate that this novel emollient can directly inhibit cutaneous inflammation in murine models of both acute irritant contact dermatitis and acute allergic contact dermatitis. However, whether this emollient could also alleviate eczematous dermatitis in humans remains to be explored.

Recent studies have demonstrated that commensal bacterial metabolites benefit human health. Because of the crucial role of the epidermal permeability barrier in cutaneous and extracutaneous function, we assessed whether the topical applications of N-palmitoyl serinol (NPS) would improve the epidermal permeability barrier in murine skin. Our results show that the topical application of 0.5% NPS in ethanol twice daily for 1 week lowered basal transepidermal water loss rates and accelerated barrier recovery in normal mice. Moreover, topical NPS prevented the emergence of epidermal permeability barrier dysfunction in a murine model of allergic contact dermatitis. These results suggest that topical NPS could be used to prevent or treat skin disorders characterized by inflammation and an abnormal epidermal permeability barrier.Des études récentes ont démontré que les métabolites des bactéries commensales sont bénéfiques pour la santé humaine. En raison du rôle crucial de la barrière de perméabilité épidermique dans la fonction cutanée et extra-cutanée, nous avons évalué si les applications topiques de N-palmitoyl sérinol (NPS) amélioreraient la barrière de perméabilité épidermique dans la peau murine. Nos résultats montrent que l’application topique de 0,5 % de NPS dans de l’éthanol deux fois par jour pendant 1 semaine a réduit les taux de base de perte d’eau trans-épidermique et accéléré la récupération de la barrière chez les souris normales. De plus, le NPS topique a empêché l’émergence d’un dysfonctionnement de la barrière de perméabilité épidermique dans un modèle murin de dermatite de contact allergique. Ces résultats suggèrent que le NPS topique pourrait être utilisé pour prévenir ou traiter les troubles cutanés caractérisés par une inflammation et une barrière de perméabilité épidermique anormale.(Traduit par Docteur Serge Messier).

Yiping Zhong,* Lining Huang,* Tingting Yan, Yongjun Chen, Bin Yang, Mao-Qiang Man Aesthetic Department, Dermatology Hospital, Southern Medical University, Guangzhou, Guangdong 510091, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mao-Qiang Man; Bin YangDermatology Hospital, Southern Medical University, Guangzhou 510091, People’s Republic of ChinaTel+86-20-87257353Email mqman@hotmail.com; yangbin101@hotmail.comBackground: Hori’s nevus is a common pigmented disorder on the face, preferentially in females. The clinical features have not been well characterized.Aim: To characterize the clinical features of Hori’s nevus in Chinese adults.Subjects and Methods: Data were collected from files of patients who visited our hospital from 2015 to 2018. Age- and disease duration-related characteristics were analyzed.Results: A total of 497 patients, including 486 females and 11 males, were included in this analysis. One fifth of the patients had a family history of Hori’s nevus. Over 70% of patients were aged 21– 30 years. Age at onset was comparable between males and females (20.64 ± 1.01 vs 18.99 ± 0.24). Out of 497 subjects, 218 subjects (44%) displayed yellow-brown lesions while blue-brown lesions wwere observed in 103 subjects (21%). The rest (176 cases, 35%) showed slate-grey lesions. Involvement in the zygomatic area was observed in 496/497 subjects. Involvement in a single area accounted for 74% of patients, while two areas were involved in 19% of patients. The number of involved areas correlated positively with disease duration. However, the proportion of subjects with yellow-brown lesions correlated negatively with disease duration, while the proportion of subjects with slate-grey lesions correlated positively with disease duration. The proportion of subjects with lesions involving the lower eyelids, the root of the nose, the temple and the outer frontal area correlated positively with age.Conclusion: Hori’s nevus mainly involves the zygomatic area in subjects aged 21– 30 years. Lesion color is associated with age, age at onset, and disease duration.Keywords: Hori’s nevus, age, pigmentation

Summary Inflammatory response heterogeneity has impeded high-resolution dissection of diverse immune cell populations during activation. We characterize mouse cutaneous immune cells by single-cell RNA sequencing, after inducing inflammation using imiquimod and oxazolone dermatitis models. We identify 13 CD45+ subpopulations, which broadly represent most functionally characterized immune cell types. Oxazolone pervasively upregulates Jak2/Stat3 expression across T cells and antigen-presenting cells (APCs). Oxazolone also induces Il4/Il13 expression in newly infiltrating basophils, and Il4ra and Ccl24, most prominently in APCs. In contrast, imiquimod broadly upregulates Il17/Il22 and Ccl4/Ccl5. A comparative analysis of single-cell inflammatory transcriptional responses reveals that APC response to oxazolone is tightly restricted by cell identity, whereas imiquimod enforces shared programs on multiple APC populations in parallel. These global molecular patterns not only contrast immune responses on a systems level but also suggest that the mechanisms of new sources of inflammation can eventually be deduced by comparison to known signatures., Graphical Abstract, Highlights • Oxazolone pervasively upregulates Jak2/Stat3 expression across T cells and APCs • Il4/Il13 induction in skin by oxazolone is dominated by infiltrating basophils • Imiquimod broadly increases Il17/Il22 and Ccl4/Ccl5, extending to non-T cells • Oxazolone induces more highly compartmentalized immune cell responses than imiquimod, Immunology; Systems Biology

Nitric oxide (NO) regulates a variety of epidermal functions, including epidermal proliferation, differentiation and cutaneous wound healing. However, whether nitric oxide (NO) and its synthetic enzymes regulate epidermal permeability barrier homeostasis is not clear. In the present study, we employed inducible nitric oxide synthase (iNOS) KO mice to explore the role of iNOS in epidermal permeability barrier homeostasis. Our results showed that iNOS mice displayed a comparable levels of basal transepidermal water loss rates, stratum corneum hydration and skin surface pH to their wild-type mice, but epidermal permeability barrier recovery was significantly delayed both 2 and 4hours after acute barrier disruption by tape stripping. In parallel, expression levels of mRNA for epidermal differentiation-related proteins and lipid synthetic enzymes were lower in iNOS KO mice versus wild-type controls. Topical applications of two structurally unrelated NO donors to iNOS KO mice improved permeability barrier recovery kinetics and upregulated expression levels of mRNA for epidermal differentiation-related proteins and lipid synthetic enzymes. Together, these results indicate that iNOS and its product regulate epidermal permeability barrier homeostasis in mice.

Introduction: Either systemic or topical glucocorticoids (GCs) can cause significant adverse effects on cutaneous structure and function. Although some products and ingredients can improve GC-induced abnormalities in epidermal permeability barrier, the efficacy is moderate. Prior studies in normal mice showed that topical applications of a heparinoid-containing product, Hirudoid® cream, improve epidermal barrier function by upregulation of epidermal proliferation, expression of mRNA for epidermal differentiation, and lipid production. Objective: The objective of this study was to assess whether topical applications of this product could prevent GC-induced changes in epidermal function in murine skin. Materials and Methods: One group of C57BL/6J mice was treated topically with 0.05% clobetasol propionate twice daily for 6 days, while another group was treated topically with Hirudoid® cream 30 min after each application of clobetasol propionate. Untreated mice served as normal controls. Transepidermal water loss (TEWL) rates, stratum corneum hydration, and skin surface pH were measured using respective probes connected to an MPA5 physiology monitor. qPCR was used to measure the expression levels of mRNA for keratinocyte differentiation-related proteins and lipid synthetic enzymes. Results: Co-applications of Hirudoid® cream with GC minimally, but significantly, increased skin thickness in comparison to GC treatment alone (p < 0.05), in parallel with increased expression levels of mRNA for PCNA in both the dermis and the epidermis. Moreover, Hirudoid® cream largely prevented GC-induced elevation in basal TEWL (p < 0.001) and delay in barrier recovery (p < 0.05), accompanied by upregulation in the expression levels of mRNA for epidermal involucrin, HMGCoA, and SPT1. However, both stratum corneum hydration and skin surface pH were comparable in the skin treated with GC alone versus GC + Hirudoid® cream. Conclusion: Topical heparinoid-containing product can partially prevent GC-induced alterations in some epidermal functions.

Chronologically-aged skin displays multiple functional changes in both the dermis and the epidermis. It appears that epidermal dysfunction, compromised permeability homeostasis, reduced stratum corneum hydration and elevated skin surface pH predispose to the development of aging-associated cutaneous and extracutaneous disorders. Improvements in epidermal function have been shown to be an effective alternative therapy in the prevention and treatment of some aging-associated cutaneous disorders, including eczematous dermatitis, pruritus, and xerosis. Recent studies demonstrated that epidermal dysfunction leads to the development of chronic, low-grade systemic inflammation, termed 'inflammaging,' which is linked to the development of aging-associated systemic disorders. Thus, correction of epidermal dysfunction could comprise a novel strategy in the prevention and treatment of aging-associated systemic disorders as well. In this review, we summarize aging-associated alterations in epidermal function, their underlying mechanisms, and their clinical significance. Regimens to improve epidermal function in the elderly are also discussed.

Epidermal biophysical properties can be affected by many factors, including body site, age, gender, ethnicity, disease, temperature, humidity, and ultraviolet (UV) radiation. Information about variation of epidermal biophysical properties with seasons is still limited. In the present study, we determined seasonal variation of epidermal biophysical properties of women in Kunming, China.A total of 72 women, aged 22.96 ± 2.11 years, were enrolled in this study. Transepidermal water loss rates (TEWL), stratum corneum (SC) hydration, sebum content, melanin index (MI), erythema index (EI), and L*a* values were measured on the right cheek and the right forearm, using a non-invasive skin physiological instrument in the spring, summer, autumn, and winter in Kunming, China.On the cheek, TEWL, SC hydration, sebum, MI, and L*a* values varied greatly with seasons (P .05). SC hydration, sebum, MI, and a*value peaked in the summer, but went lowest in winter. In contrast, TEWL and L*value went lowest in summer but peaked in winter. Similarly, SC hydration, MI, and L*value also varied with seasons on the forearm (P .05). In addition, SC hydration, sebum, MI, EI, and a*value of the cheek were higher than that of the forearm (P .001), but L*values of the cheek were lower than that of the forearm (P .001). There were no correlations among TEWL and MI, EI, and L*a*values in any season (P .05).Both epidermal permeability barrier function, sebum, and skin pigment in healthy women vary seasons in Kunming, China.

Protective role of the skin is against external insults and maintenance of electrolyte homeostasis of the body. Cutaneous dysfunction can account for the development of both cutaneous and systemic disorders. Thus, improvements in cutaneous functions can benefit a number of extracutaneous and cutaneous functions. Resveratrol, a natural ingredient, displays multiple benefits for various systems/organs, including the skin. The benefits of resveratrol for cutaneous functions include stimulation of keratinocyte differentiation and antimicrobial peptide expression, inhibition of keratinocyte proliferation and cutaneous inflammation, UV protection, anticancer, antiaging, and inhibition of melanogenesis. The mechanisms of action of resveratrol include activation of sirtuin 1 and nuclear factor erythroid 2-related factor 2, and inhibition of mitogen-activated protein kinase signaling. Evidence suggests that topical resveratrol could be a valuable alternative not only for daily skin care, but also for the prevention and treatment of various cutaneous disorders. This review summarizes the benefits of resveratrol for cutaneous functions.

BACKGROUND: Adverse skin reactions to skin care products have been increasing in recent years. However, these reactions have not been characterized well to date. OBJECTIVE: To describe symptoms, clinical signs and frequency of adverse cutaneous reactions to skin care products on the face in males vs. females of various ages. PATIENTS AND METHODS: All outpatients diagnosed with adverse cutaneous reactions to skin care products on the face examined by dermatologists at Dermatology Hospital of Southern Medical University between November 1, 2016 and October 31, 2017, employing a questionnaire and interviewed by a dermatologist, were eligible. The association of adverse cutaneous reactions with age and gender was analyzed. RESULTS: A total of 433 outpatients, accounting for 0.12% of total outpatients, were assessed. Of these, 223 patients, including 204 females and 19 males, aged 4 to 75 years old, were eventually diagnosed with adverse reactions to skin care products on the face. Eighty-two per cent of patients experienced pruritus, while 80% showed erythema, and 48% visible swelling. The incidences of both xerosis and edema correlated positively with age, while acne-like lesions were negatively associated with age, but not with gender. CONCLUSIONS: Our results indicate that pruritus, xerosis and erythema are common adverse cutaneous reactions to facial skin care products. These reactions vary with age, but not gender. Vigorous safety testing should precede marketing of skin care products.

BACKGROUND. Adverse cutaneous reactions to skin care products (SCP) are becoming increasingly common, and may be indicative of defective permeability barrier function. AIM. To determine the differences in transepidermal water loss rates (TEWL) between skin patch positive versus negative to skin care products in normal Chinese females. METHODS. Skin patch test reactions to nine skin care products were assessed in 65 normal Chinese females. Correlations of cutaneous reactions to a panel of nine foreign and domestic SCP with permeability barrier function and stratum corneum (SC) hydration levels were analyzed. RESULTS. Out of 65 subjects, 24 (37%) displayed positive reactions to one or more SCP. However, the occurrence of positive reactions to patch tests did not correlate with either transepidermal water loss rates or SC hydration levels. CONCLUSIONS. Though a substantial proportion of normal females display adverse reactions to SCP, this problem cannot be attributed to differences in the qualities of their epidermal permeability barriers, and therefore, these reactions more likely reflect the potential adverse events of the SCP themselves. However, further studies in large cohort of both males and females would be helpful to ascertain whether TEWL levels can predict cutaneous reactions to SCP.

Background Becker's nevus is a common skin disorder. Lasers and light instruments are the major modalities for the treatment of Becker's nevus, but the outcomes were mixed. Objective To evaluate the efficacy of the intense pulsed light for Becker's nevus in a large Chinese cohort. Methods We retrospectively analyzed the efficacy of the intense pulsed light for Becker's nevus in a single center. Results A total of 45 patients, including 26 males and 19 females (male to female ratio = 1.4), aged 5-42 years, were included in this analysis. Twenty-seven patients (60%) were with hypertrichosis. Treatments with intense pulsed light resulted in over 75% improvements in pigmentation and hair density in 1 and 2 cases, respectively. One patient displayed 51%-75% reductions in hair density. The rest displayed ≤50% improvements in pigmentation and hair density. Recurrence occurred in all cases within 6 months after the last treatment. Adverse reactions were temporary and mild hypopigmentation, hyperpigmentation, hypertrophic scar, pain, and erythema. Conclusion Intense pulsed light does not exhibit long-term benefits for Becker's nevus. Further studies in the large cohort are still required to validate the present results. Moreover, whether changes in the treatment parameters can improve the efficacy of intense pulsed light remains to be explored.

Pigmentation evolved in ancestral humans to protect against toxic, ultraviolet B irradiation, but the question remains: “what is being protected?” Because humans with dark pigmentation display a suite of superior epidermal functions in comparison with their more lightly pigmented counterparts, we hypothesized and provided evidence that dark pigmentation evolved in Africa to support cutaneous function. Because our prior clinical studies also showed that a restoration of a competent barrier dampens cutaneous inflammation, we hypothesized that resistance to inflammation could have provided pigmented hominins with yet another, important evolutionary benefit. We addressed this issue here in two closely related strains of hairless mice, endowed with either moderate (Skh2/J) or absent (Skh1) pigmentation. In these models, we showed that (a) pigmented mice display a markedly reduced propensity to develop inflammation after challenges with either a topical irritant or allergen in comparison with their nonpigmented counterparts; (b) visible and histologic evidence of inflammation was paralleled by reduced levels of pro‐inflammatory cytokines (i.e., IL‐1α and INFα); (c) because depigmentation of Skh2/J mouse skin enhanced both visible inflammation and pro‐inflammatory cytokine levels after comparable pro‐inflammatory challenges, the reduced propensity to develop inflammation was directly linked to the presence of pigmentation; and (d) furthermore, in accordance with our prior work showing that pigment production endows benefits by reducing the surface pH of skin, acidification of albino (Skh1) mouse skin also protected against inflammation, and equalized cytokine levels to those found in pigmented skin. In summary, pigmentation yields a reduced propensity to develop inflammation, consistent with our hypothesis that dark pigmentation evolved in ancestral humans to provide a suite of barrier‐linked benefits that now include resistance to inflammation.